The Internal Impermeant Anion, Its Mean Valence and Osmolarity-Charge Asymmetry

Background/Aims: For many years experimental and theoretical studies of the processes controlling the transmembrane potential of living cells and their volume were focused on ions, first of all Na+, K+, and Cl-, that can be moved in and out of the cell by various active and passive mechanisms. But recently more and more attention has been directed toward the internal impermeant anion (Xz-) – a complex entity that is comprised of many very different molecules. The most intriguing feature of the internal impermeant anion is that its amount and, importantly, its mean valence can be changed during the metabolic activity of the cell. The aim of this paper is to computationally investigate how changes in the amount and the mean valence of the internalimpermeant anion influence the concentration of the main ions, the membrane potential, and the cell volume. Methods: The computational analyses were performed using our charge-difference model describe earlier. Results and Conclusion: The results of computational simulations confirm previous results that changes in the amount of Xz- influence nothing but the cell volume if z remains constant, although transient disturbances of concentrations and Em happen and their extent depends on the speed of Xz- changes. Changes of z have more serious consequences. A decrease of |z| leads to a decrease of concentrations of cations ([K+]i and [Na+]i), to an increase of the concentrations of anions ([Cl-]I and [Xz-]i), and to depolarization of the cell membrane; an increase of |z| leads to changes in the opposite directions. Interestingly, even in conditions when Xz- remains unchanged, the normal electrophysiological activity expressed in changes of Em will affect [Cl-]i and consequently [Xz-]i (due to volume changes), inducing feedback effects on the cation concentrations and Em. Accordingly, Xz- is viewed as an important but not the only component of a broader concept of osmolarity-charge asymmetry. The basic physical reasons that determine the interrelations between Xz- on one hand and ionic concentrations, Em, and the cell volume on the other hand are discussed.